Patent IL-98319-A (IL)
Title: Sulphurous derivatives of imidazole, their preparation process, and pharmaceutical compositions containing them
IPC: A61K31/4178
Filed: 1991-05-31
Abstract: Angiotensin II receptor antagonistic compounds of the formula R1 N R2B N (CH2)m R3B YB in which: R1 represents an alkyl, alkenyl, alkynyl, or alkylthio radical, each of these radicals being linear or branched and containing at most 10 carbon atoms, or a cycloalkyl radical containing 3 to 7 carbon atoms, all these radicals being optionally substituted by one or more identical or different radicals chosen from halogen atoms, and the following radicals, hydroxy, alkoxy containing at most 6 carbon atoms, alkylthio, acyl, free, salified or esterified carboxy, cyano, nitro, amino optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms, cycloalkyl containing 3 to 7 carbon atoms and aryl optionally substituted by one or more identical or different radicals chosen from halogen atoms, and the following radicals, hydroxyl, alkyl, alkenyl and alkoxy containing at most 6 carbon atoms, haloalkyl, alkylthio, haloalylthio, haloalkoxy, aryloxy, arylalkoxy, carbamoyl, acyl, acyloxy, free, salified or esterified carboxy, tetrazolyl, cyano, nitro, amino optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms and phenyl optionally substituted by one or more radicals chosen from halogen atoms, and the following radicals, hydroxyl, alkyl and alkoxy containing at most 4 carbon atoms, trifluoromethyl, free, salified or esterified carboxy and tetrazolyl, R2B and R3B' identical or different, are chosen from: (a) the following radicals: mercapto, formyl, acyl, free, salified or esterified carboxy, nitro, cyano, -PO3 (R)2 in which R represents a hydrogen atom, an alkyl or aryl radical, amino or carbamoyl radicals optionally substituted by one or two radicals chosen from the -(CH2)m1- S (O)m2 -X-R10 radicals as defined below and alkyl and alkinyl radicals, having at most 4 carbon atoms, (b) the radicals R4B, -S (O)nR4B, O -S-R4B and -OR4B N-S (O)n -X( in which: n represents the values 0, 1 or 2, X( represents an aryl radical optionally substituted by one or more identical or different radicals chosen from halogen atoms, the following radicals: hydroxyl, alkyl, alkenyl and alkoxy containing at most 6 carbon atoms, haloalkyl, alkylthio, haloalkylthio, haloalkoxy, aryloxy, arylalkoxy, carbamoyl, acyl, acyloxy, free, salified or esterified carboxy, tetrazolyl, cyano, nitro, amino optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms and phenyl optionally substituted by one or more radicals chosen from halogen atoms, and the following radicals: hydroxyl, alkyl and alkoxy containing at most 4 carbon atoms, trifluoromethyl, free, salified or esterified carboxy and tetrazolyl, and either R4B represents a -(CH2)m1 -S(O)m2 -X-R10 radical in which ml represents an integer from 0 to 4, m2 represents an integer from 0 to 2, preferably 2, and either when ml is not 0, X-R10 represents an amino radical optionally substituted by one or two alkyl radicals containing at most 6 carbon atoms, or whatever the value of ml, X represents a single bond or the radicals -NH-, -NH-CO- and -NH-CO-NH-, and R10 represents an alkyl, alkenyl or aryl radical, these radicals being optionally substituted by one or more identical or different radicals chosen from halogen atoms, and the following radicals: hydroxyl, alkoxy containing at most 6 carbon atoms, alkylthio, acyl, free, salified or esterified carboxy, cyano, nitro, amino optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms, cycloalkyl containing 3 to 7 carbon atoms and aryl optionally substituted by one or more identical or different radicals chosen from halogen atoms, the radicals hydroxyl, alkyl, alkenyl and alkoxy containing at most 6 carbon atoms, haloalkyl, alkylthio, haloalkylthio, haloalkoxy, aryloxy, arylalkoxy, carbamoyl, acyl, acyloxy, free, salified or esterified carboxy, tetrazolyl, cyano, nitro, amino optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms and phenyl optionally substituted by one or more radicals chosen from halogen atoms, hydroxyl radicals, alkyl and alkoxy radicals containing at most 4 carbon atoms, trifluoromethyl radicals, free, salified or esterified carboxy radicals and tetrazolyl radicals, or R4B represents the hydrogen atom, or radicals chosen from alkyl, alkenyl, alkynyl and acyl, each of these radicals being linear or branched and containing at most 6 carbon atoms, and being optionally interrupted by one or more heteroatoms chosen from sulphur, oxygen or nitrogen atoms, or R4B represents an amino radical optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms or an aryl radical, the alkyl alkenyl, cycloalkyl and aryl radicals being optionally substituted by one or more identical or different radicals chosen from: - halogen atoms, - hydroxyl, haloalkyl, alkylthio, alkenylthio, alkynylthio, mercapto, acylthio, haloalkylthio, haloalkoxy, cyano, azido, nitro radicals, - the -O-Si (R5)3 or -Si (R5)3 radical in which R5 represents an alkyl radical containing at most 4 carbon atoms, - aryl, arylalkyl, arylalkenyl, arylthio, aryloxy and arylalkoxy radicals in which, if appropriate, the alkyl, alkenyl and alkoxy radicals contain at most 6 carbon atoms and the aryl radical is optionally substituted by one or more identical or different radicals chosen from halogen atoms, hydroxyl, alkyl, alkenyl and alkoxy radicals containing at most 6 carbon atoms, haloalkyl, alkylthio, haloalkylthio, haloalkoxy, aryloxy, arylalkoxy, carbamoyl, acyl, acyloxy, free, salified or esterified carboxy, tetrazolyl, cyano, nitro, amino optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms and phenyl optionally substituted by one or more radicals chosen from halogen atoms, hydroxyl radicals, alkyl and alkoxy radicals containing at most 4 carbon atoms, trifluoromethyl radicals, free, salified or esterified carboxy radicals and tetrazolyl radicals, alkyl, alkenyl and alkoxy radicals containing at most 6 carbon atoms, free, salified or esterified carboxy radicals, tetrazolyl, acyl, formyl, acyloxy, -SO3H radicals, and -CO-Nand-N R6 R8 the radicals R7 R9 in which: either R6 and R7 or R8 and R9, identical or different, are chosen from: the hydrogen atom, amino acids, alkyl and alkenyl radicals containing at most 6 carbon atoms and optionally substituted by one or more indentical or different radicals chosen from halogen atoms, the hydroxyl radical or alkoxy radicals containing at most 6 carbon atoms, the aryl, arylalkyl and arylalkenyl radicals in which the linear or branched alkyl and alkenyl radicals contain at most 6 carbon atoms, these aryl, arylalkyl and arylalkenyl radicals being such that the aryl radical that they constitute or that they contain represents a monocyclic radical containing 5, 6 or 7 links or a radical constituted by condensed rings containing 8 to 14 links, these radicals containing optionally one or more heteroatoms chosen from oxygen, nitrogen and sulphur atoms, and being optionally substituted by one or more radicals chosen from halogen atoms, hydroxyl, nitro radicals, alkyl, alkenyl, haloalkyl, alkoxy and acyl radicals, these radicals containing at most 6 carbon atoms, amino radicals optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms, free, salified or esterified carboxy radicals, tetrazolyl, aryl and arylalkyl radicals, these two latter radicals being optionally substituted by one or more radicals chosen from halogen atoms, hydroxyl, trifluoro- methyl, nitro radicals, free, salified or esterified carboxy radicals and tetrazolyl radicals, - a- (CH2)m1 -S (O)m2 -X-R10 radical as defined above, or R6 and R7 or R8 and R9 form respectively with the nitrogen atom to which they are linked a monocyclic radical containing 5, 6 or 7 links or a radical constituted by condensed rings containing 8 to 14 links, these identical or different radicals optionally containing one or more other heteroatoms chosen from oxygen, nitrogen and sulphur atoms, and being optionally substituted by one or more radicals chosen from halogen atoms, hydroxyl radicals, nitro, alkyl, alkenyl, haloalkyl, alkoxy and acyl radicals, these radicals containing at most 6 carbon atoms, amino radicals optionally substituted by one or two identical or different alkyl radicals containing at most 6 carbon atoms, free, salified or esterified carboxy radicals, tetrazolyl, aryl and arylalkyl radicals, these two latter radicals being optionally substituted by one or more radicals chosen from halogen atoms, hydroxyl radicals, trifluoromethyl, nitro radicals, free, salified or esterified carboxy radicals and tetrazolyl radicals, or R8 and R9, identical or different, represent an acyl radical or one of R8 or R9 represents a carbamoyl, alkoxycarbonyl or benzyloxycarbonyl radical or R8 and R9 form together with the nitrogen atom to which they are linked a phthalimido or succinimido radical, c) the -S-S-R4B' radical in which R4B' represents the values defined for R4B except for the amino and alkoxy radicals, it being understood that at least one of R2B and R3B represents the -OR4B radical or one of the radicals: O -S (O)n R4B -S-R4B or -S-S-R4B( N-2 (O)n -X knowing that R2B and R3B cannot represent simultaneously the - S-S-R4B' radical, m represents the value 0, 1 or 2, YB represents the -Y1B -B-Y2B radical in which: Y1B represents a monocyclic aryl radical containing 5, 6 or 7 links or constituted by condensed rings containing 8 to 10 links, these radicals optionally containing one or more heteroatoms chosen from oxygen, nitrogen and sulphur atoms, and being optionally substituted by one or more radicals chosen from the radicals that can be represented by R2B and R3B